The Effect of Bariatric Surgery on Microvascular Structure and Function, Peripheral Pressure Waveform and General Cardiovascular Risk: A Longitudinal Study.

PURPOSE: This study aims to assess the effect of bariatric surgery on retinal microvascular calibre, peripheral microvascular function, peripheral pressure waveforms, and the general cardiovascular disease (CVD) risk in obese individuals after undergoing Roux-en-Y gastric bypass (RYGB) surgery. METHODS: A total of 29 obese participants were included in the study. All of the measurements were conducted at two time points: before and one year following the bariatric surgery procedure. General anthropometric data, as well as blood markers for glucose, cholesterol, and triglycerides were assessed in all individuals. In all participants, the Framingham risk score (FRS), and retinal vessel calibre measurements, using a Zeiss fundus camera and VesselMap software (ImedosSystems, Jena, Germany), were performed. Systemic arterial stiffness was measured by pulse wave analysis (PWA), and peripheral microvascular reactivity by way of digital thermal monitoring (DTM) in all participants. RESULTS: As expected, various general anthropometric parameters, including body mass index (BMI), waist circumference and neck circumference, were significantly decreased post-surgery comparing to baseline in all individuals (all p < 0.001). In addition, their general CVD risk, as measured using FRS, was significantly improved (p < 0.001). At the retinal vascular level, central retinal artery equivalent (CRAE) as well as, central retinal vein equivalent (CRVE) had increased after surgery comparing to the baseline values (p = 0.003 and p = 0.007, respectively). In addition, both systemic arterial stiffness and peripheral microvascular reactivity had improved in all participants (p < 0.001 and p = 0.008 respectively). CONCLUSIONS: Our findings suggest that bariatric surgery has a positive effect on the overall vascular health, as well as on the general CVD risk of the obese patients undergoing this procedure.

Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk.

Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30−55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1: <5%­n = 53) or a normal FMD response (group 2: 7−10%­n = 47). Results: Individuals exhibiting reduced FMD responses showed a reduced baseline-corrected microvascular arterial dilation response to flickering light (p = 0.039). In addition, they also exhibited a reduced arteriolar maximum dilation (p = 0.034), as well as a longer dilation reaction time (p = 0.048) and a lower dilation amplitude (p = 0.042) when compared to those with normal FMD values. Conclusion: In otherwise healthy middle-aged individuals, early signs of vascular dysfunction are reflected simultaneously at both macro- and microvascular levels.

Retinal Microvascular Dysfunction Occurs Early and Similarly in Mild Alzheimer's Disease and Primary-Open Angle Glaucoma Patients.

Purpose: To assess the similarities and differences in retinal microvascular function between mild Alzheimer's disease (AD) patients, early-stage primary open angle glaucoma (POAG) patients and healthy controls. Methods: Retinal vessel reactivity to flickering light was assessed in 10 AD, 19 POAG and 20 healthy age matched control patients by means of dynamic retinal vessel analysis (DVA, IMEDOS, GmbH, Jena, Germany) according to an established protocol. All patients additionally underwent BP measurements and blood analysis for glucose and lipid metabolism markers. Results: AD and POAG patients demonstrated comparable alterations in retinal artery reactivity, in the form of an increased arterial reaction time (RT) to flicker light on the final flicker cycle (p = 0.009), which was not replicated by healthy controls (p > 0.05). Furthermore, the sequential changes in RT on progressing from flicker one to flicker three were found to differ between healthy controls and the two disease groups (p = 0.001). Conclusion: AD and POAG patients demonstrate comparable signs of vascular dysfunction in their retinal arteries at the early stages of their disease process. This provides support for the concept of a common underlying vascular aetiology in these two neurodegenerative diseases.

The Use of Retinal Microvascular Function and Telomere Length in Age and Blood Pressure Prediction in Individuals with Low Cardiovascular Risk.

Ageing represents a major risk factor for many pathologies that limit human lifespan, including cardiovascular diseases. Biological ageing is a good biomarker to assess early individual risk for CVD. However, finding good measurements of biological ageing is an ongoing quest. This study aims to assess the use retinal microvascular function, separate or in combination with telomere length, as a predictor for age and systemic blood pressure in individuals with low cardiovascular risk. In all, 123 healthy participants with low cardiovascular risk were recruited and divided into three groups: group 1 (less than 30 years old), group 2 (31-50 years old) and group 3 (over 50 years old). Relative telomere length (RTL), parameters of retinal microvascular function, CVD circulatory markers and blood pressure (BP) were measured in all individuals. Symbolic regression- analysis was used to infer chronological age and systemic BP measurements using either RTL or a combination of RTL and parameters for retinal microvascular function. RTL decreased significantly with age (p = 0.010). There were also age-related differences between the study groups in retinal arterial time to maximum dilation (p = 0.005), maximum constriction (p = 0.007) and maximum constriction percentage (p = 0.010). In the youngest participants, the error between predicted versus actual values for the chronological age were smallest in the case of using both retinal vascular functions only (p = 0.039) or the combination of this parameter with RTL (p = 0.0045). Systolic BP was better predicted by RTL also only in younger individuals (p = 0.043). The assessment of retinal arterial vascular function is a better predictor than RTL for non-modifiable variables such as age, and only in younger individuals. In the same age group, RTL is better than microvascular function when inferring modifiable risk factors for CVDs. In older individuals, the accumulation of physiological and structural biological changes makes such predictions unreliable.

Retinal Microvascular Abnormalities and Systemic Arterial Stiffness Are the First Manifestation of Cardiovascular Abnormalities in Patients with Untreated Moderate to Severe Obstructive Sleep Apnoea and with Low to Intermediate Cardiovascular Risk-A Pilot Study.

This study aimed to investigate macro- and microvascular function parameters and their relationship with known markers of cardiovascular risk in patients with untreated moderate to severe obstructive sleep apnoea (OSA). Fourteen patients with moderate to severe OSA and fourteen controls were included in the present study. General assessments included BMI, systemic blood pressure (BP) and circulating markers for oxidative stress and endothelial function. Additional assessments included 24 h BP and heart rate monitoring, as well as the assessment of heart rate variability. Macro- and microvascular assessments included augmentation index, carotid intima-media thickness, brachial artery flow-mediated dilation, as well as various retinal microvascular function assessments, using the Dynamic Retinal Vessel Analyzer. All participants completed the Short Form Health Survey, Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness Scale. The results show that, in comparison to controls, BMI (p = 0.003) and AIx (p = 0.025) were significantly higher in the OSA group. There was, however, no significant difference between groups with regard to other measured systemic general, vascular and circulatory parameters (all p > 0.05). Nevertheless, the retinal microvascular function showed various alterations in the OSA patients, including a delayed reaction time in response to flicker (p = 0.047), as well as a decreased dilation amplitude (p = 0.004), dilation slope (p = 0.004), and post-flicker constriction (p = 0.015). In addition, the observed SlopeAD alterations correlated negatively with BMI values only in the OSA group (r = −0.46, p = 0.045). In conclusion, individuals with untreated moderate to severe OSA but without overt CVD, exhibit signs of increased arterial stiffness and retinal microvascular dysfunction, which can be early indicators for future vascular complications.

Impact of Bariatric Surgery-Induced Weight Loss on Anterior Eye Health in Patients with Obesity.

The aim of the present research was to assess the effect of bariatric surgery-induced weight loss on the tear film and ocular surface of patients with obesity. A total of 29 participants with obesity (aged 47.2 ± 10.1 years, 8 male) were measured at baseline and followed up one year after Roux-en-Y gastric bypass (RYGB) surgery. General anthropometric data, as well as serum lipid markers of cholesterol, were assessed in all individuals. Bilateral anterior eye measurements of tear meniscus height (TMH), non-invasive tear breakup time, bulbar and limbal redness and infrared meibography were captured using the Keratograph K5M (Oculus) and ocular surface damage was evaluated using fluorescein sodium and lissamine green staining. Bariatric surgery resulted in significant loss of weight (body mass index p < 0.001) and an improvement in the blood lipid profile (p < 0.01) in all participants. However, there were no statistically significant differences between the baseline and one-year follow-up for any of the measured clinical ocular surface and tear film variables (all p > 0.05). Although there were trends for a reduced TMH and a decrease in meibomian gland dropout after bariatric surgery, these differences were also insignificant (p > 0.05). In conclusion, weight reduction through bariatric surgery did not have an effect on the tear film or ocular surface in unselected patients with obesity.

Oxysterols and Retinal Microvascular Dysfunction as Early Risk Markers for Cardiovascular Disease in Normal, Ageing Individuals.

The aim of the present paper is to assess the relationship between oxysterol levels and retinal microvascular function in individuals of various age groups, free of clinically evident diseases. Forty-two apparently healthy individuals were included in the present study (group 1: 19-30 years, group 2: 31-50 years, and group 3: 51-70 years). Retinal microvascular function was assessed using the dynamic retinal vessel analyzer (DVA, IMEDOS GmbH, Jena, Germany). Fasting plasma was obtained from all subjects and quantification of monohydroxy and dihydroxy oxysterols assessment was performed using LC-MS/MS following reverse phase chromatography. A Griess assay was used to evaluate the Nitric Oxide (NO) concentration in all individuals. The glutathione redox ratio was also analyzed by means of whole blood glutathione recycling assay. In all participants, the levels of 7-Ketocholesterol, 25-hydroxycholesterol and 7ß-hydroxycholesterol correlated significantly and positively with the time to maximum arteriolar dilation. In addition, 25-hydroxycholesterol and 7ß-hydroxycholesterol negatively correlated to the percentage of maximum arteriolar dilation. A negative correlation was observed for 27-hydroxycholesterol and 7ß-hydroxycholesterol with microvascular arteriolar constriction. These results suggest that, with age, abnormal oxysterol levels correlate with early changes in microvascular bed function. This relationship could signal early risk for cardiovascular diseases (CVDs) in an ageing population.

Dry eye disease is associated with retinal microvascular dysfunction and possible risk for cardiovascular disease.

PURPOSE: To explore the presence of microvascular endothelial dysfunction as a measure for early cardiovascular disease in individuals diagnosed with dry eye disease (DED) as compared to age-matched normal controls. METHODS: Systemic blood pressure, Body Mass Index, intraocular pressure, blood levels of glucose (GLUC), triglycerides, cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] as well as retinal and peripheral microvascular function were assessed in twenty-five 35-50 year olds with diagnosed with DEDa (using the TFOS DEWS II criteria) and 25 age and sex-matched controls. RESULTS: After controlling all the influential covariates, individuals diagnosed with DED exhibited significant lower retinal artery baseline (p = 0.027), artery maximum diameter (p = 0.027), minimum constriction (p = 0.039) and dilation amplitude (p = 0.029) than controls. In addition, the time to reach the vein maximum diameter was significantly longer in the DED patients than in normal controls (p = 0.0052). Only in individuals diagnosed with DED, artery maximum constriction correlated statistically significantly and positively with HDL-C blood levels (p = 0.006). Similarly, artery slopeAD correlated positively with T-CHOL and LDL-C (p = 0.006 & 0.011 respectively). Additionally, artery baseline diameter and maximum constriction were significantly and negatively correlated to T-CHOL/HDL-C ratio (p = 0.032 and p = 0.013 respectively) in DED individuals only. CONCLUSIONS: Individuals with positive diagnosis of DED exhibit abnormal retinal microvascular function and possible higher risk for CVD.

Microvascular function and oxidative stress in adult individuals with early onset of cardiovascular disease.

The current study aims to investigate retinal vascular function and its relationship with systemic anti-oxidative defence capacity in normal individuals versus those with early hypertensive changes according to the current ESC/ESH guidelines. Retinal microvascular function was assessed in 201 participants by means of dynamic retinal vessel analysis. Blood pressure, lipid panel, oxidized (GSH) & reduced glutathione (GSSG) were also evaluated for each participant. Individuals classed as grade 1 hypertension demonstrated higher retinal arterial baseline diameter fluctuation (p = 0.0012), maximum dilation percentage (p = 0.0007), time to maximum constriction (p = 0.0003) and lower arterial constriction slope (p = 0.0131). Individuals classed as high normal and grade 1 hypertension also demonstrated higher time to maximum dilation than individuals classed as optimal or normal. GSH levels correlated negatively with SBP, DBP and MBP values in all participants (p = 0.0010; p = 0.0350 and p = 0.0050) as well as with MBP values in high normal and grade 1 hypertension (p = 0.0290). The levels of GSSG correlated positively with SBP, DBP and MBP values in all participants (p = 0.0410; p = 0.0330 and, p = 0.0220). Our results point to the fact that microvascular alterations can be identifiable at BP values still considered within normal values and go in parallel with the changes observed in the level of oxidative stress.

Retinal and peripheral vascular function in healthy individuals with low cardiovascular risk.

OBJECTIVE: To assess retinal and peripheral microvascular function in individuals with low cardiovascular risk. METHODS AND RESULTS: Retinal microvascular function was assessed using the dynamic vessel analyser (DVA) and peripheral vascular reactivity was measured using the digital thermal monitor (DTM) in 136 healthy participants. In addition, systemic blood pressure (BP) profiles, blood analyses for glucose and lipid metabolism markers (CHOL, HDL-c, LDL-c), as well as the Framingham Risk Score (FRS) were assessed in all participants. Based on peripheral vascular reactivity scores, participants were separated into 3 groups: high, intermediate and low risk. Participants with high risk showed a significant higher retinal arteriolar time to reach maximum dilation (tMD) than those with intermediate and low risk (p < 0.001). In addition, retinal arterial dilation amplitude (DA), and constriction slope (SlopeAC) were higher in subjects with low risk (p = 0.006, p = 0.019). Only in high risk participants, peripheral vascular reactivity parameters correlated with retinal arterial functional parameters DA, (r = 0.3800, p = 0.029) and tMD (r = -0.5904, p < 0.001). CONCLUSION: We conclude that signs of abnormal vascular function are similarly present and detectable in various microvascular beds, despite existing differences in their anatomical and physiological properties.

Retinal vascular function in asymptomatic individuals with a positive family history of cardiovascular disease.

PURPOSE: To compare retinal microvascular function in healthy individuals with and without a positive family history (FH) of cardiovascular disease (CVD). METHODS: Retinal vessel reactivity was assessed by means of dynamic retinal vessel analysis in 38 healthy subjects aged between 30 and 66 years with a positive FH of CVD and 37 age- and gender-matched control subjects. Other assessments included blood pressure (BP) profiles, blood glucose and lipid metabolism markers, Framingham risk scores (FRS), carotid intima-media thickness (c-IMT) and brachial flow-mediated dilation (FMD). RESULTS: Family history-positive subjects showed decreased retinal arterial baseline diameter fluctuation, dilation amplitude, percent dilation, and overall constriction response slope (p = 0.001; p = 0.015; p = 0.001; and p < 0.001, respectively) and increased percent constriction (p = 0.008). On the venous side, baseline-corrected flicker response and dilation response slope were decreased in the FH-positive group (p = 0.009 and p = 0.010, respectively). There were no significant differences between groups in c-IMT scores or FMD parameters (all p > 0.05). The arterial MC% correlated negatively with decreased high-density lipoprotein cholesterol (r = -0.52, p = 0.002) in only FH-positive group. CONCLUSION: Although macrovascular function is preserved in individuals with FH positive for CVD but with low FRS, there are, however, functional impairments at the retinal microvascular level that correlate with established plasma markers for cardiovascular risk.

Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk.

The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p < 0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range.

Ageing effect on flicker-induced diameter changes in retinal microvessels of healthy individuals.

PURPOSE: To compare flicker-induced retinal vessel diameter changes in varying age groups with low cardiovascular risk. METHODS: Retinal vascular reactivity to flicker light was assessed by means of dynamic retinal vessel analysis in 57 participants aged 19-30 years, 75 participants aged 31-50 years and 62 participants aged 51-70 years participants. Other assessments included carotid intima-media thickness (c-IMT), augmentation index (AIx), blood pressure profiles, blood lipid metabolism markers and Framingham risk scores (FRS). RESULTS: Retinal arterial dilation amplitude (DA) and postflicker percentage constriction (MC%) were significantly decreased in the oldest group compared to the middle-aged (p = 0.028; p = 0.021) and youngest group (p = 0.003; p = 0.026). The arterial constriction slope (SlopeAC ) was also decreased in the oldest group compared to the youngest group (p = 0.027). On the venous side, MC% was decreased in the middle-aged and oldest groups in comparison with the youngest group (p = 0.015; p = 0.010, respectively). Additionally, men exhibited increased arterial DA (p = 0.007), and percentage dilation (MD%, p < 0.001) in comparison with women, but only in the youngest age group. Both AIx and c-IMT scores increased with age (both p < 0.001); however, no correlations were found between the observed differences in the measured retinal vascular function and systemic parameters. CONCLUSION: In individuals with low cardiovascular risk, there are age-related differences in flicker-induced retinal vessel diameter changes throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the arterial dilatory phase and are only present in young individuals.

Systemic circulatory influences on retinal microvascular function in middle-age individuals with low to moderate cardiovascular risk.

PURPOSE: To investigate the relationship between retinal microvascular reactivity, circulatory markers for CVD risk and systemic antioxidative defence capacity in healthy middle-aged individuals with low to moderate risk of CVD. METHODS: Retinal vascular reactivity to flickering light was assessed in 102 healthy participants (46-60 years) by means of dynamic retinal vessel analysis (DVA). Other vascular assessments included carotid intima-media thickness (C-IMT) and blood pressure (BP) measurements. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood glutathione levels in its reduced (GSH) and oxidized (GSSG) forms were also determined for each participant, along with Framingham risk scores (FRS). RESULTS: Retinal arterial baseline diameter fluctuation (BDF) was independently, significantly and negatively influenced by LDL-C levels (ß = -0.53, p = 0.027). Moreover, the arterial dilation slope (SlopeAD ) was independently, significantly and positively associated with redox index (GSH: GSSG ratio, ß = 0.28, p = 0.016), while the arterial constriction slope (SlopeAC ) was significantly and negatively influenced by blood GSH levels (ß = -0.20, p = 0.042), and positively associated with FRS (ß = 0.25, p = 0.009). Venous BDF and dilation amplitude (DA) were also negatively influenced by plasma LDL-C levels (ß = -0.83, p = 0.013; and ß = -0.22, p = 0.028, respectively). CONCLUSIONS: In otherwise healthy individuals with low to moderate cardiovascular risk, retinal microvascular dilation and constriction responses to stress levels are influenced by systemic antioxidant capacity, and circulating markers for cardiovascular risk.

Patients with early age-related macular degeneration exhibit signs of macro- and micro-vascular disease and abnormal blood glutathione levels.

BACKGROUND: This pilot study aimed to investigate systemic and retinal vascular function and their relationship to circulatory markers of cardiovascular risk in early age-related macular degeneration (AMD) patients without any already diagnosed systemic vascular pathologies. METHODS: Fourteen patients diagnosed with early AMD and 14 age- and gender-matched healthy controls underwent blood pressure, carotid intima-media thickness (C-IMT) and peripheral arterial stiffness measurements. Retinal vascular reactivity was assessed by means of dynamic retinal vessel analysis (DVA) using a modified protocol. Blood analyses were conducted for glutathione levels and plasma levels of total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). RESULTS: The AMD patients showed significantly greater C-IMT (p = 0.029) and augmentation index (AIx) (p = 0.042) than the age-matched controls. In addition, they demonstrated a shallower retinal arterial dilation slope (Slope AD) (p = 0.005) and a longer retinal venous reaction time (RT) to flickering light (p = 0.026). Blood analyses also revealed that AMD patients exhibited higher oxidized glutathione (GSSG) (p = 0.024), lower redox index (p = 0.043) and higher LDL-C (p = 0.033) levels than the controls. Venous RT parameter correlated positively with blood GSSG levels (r = 0.58, p = 0.038) in AMD subjects, but not in the controls (p > 0.05). CONCLUSIONS: Patients diagnosed with early AMD exhibit signs of systemic and retinal vascular alterations that correlated with known risk markers for future cardiovascular morbidity.

Reduction in blood glutathione levels occurs similarly in patients with primary-open angle or normal tension glaucoma.

PURPOSE: To investigate in parallel the systemic glutathione levels of patients suffering from primary open angle glaucoma (POAG) or normal tension glaucoma (NTG) with comparable functional loss. METHODS: Thirty-four POAG patients, 30 NTG patients, and 53 controls were subjected to blood analysis to detect the level of circulating glutathione in its reduced (GSH) and oxidized (GSSG) forms. Systemic blood pressure (BP) and ocular perfusion pressure (OPP) parameters were also determined. RESULTS: Independent of age, POAG and NTG patients demonstrated significantly lower GSH and t-GSH levels than age-matched controls (P < 0.001). Additionally, a lower redox index was found, but in POAG patients only, in comparison to both NTG and control groups (P = 0.020). GSSG levels were, however, similar between all study groups (P > 0.05). CONCLUSIONS: This study demonstrates, for the first time, that both POAG and NTG patients exhibit lower GSH and t-GSH levels than age-matched controls, indicating a similar general compromise of the antioxidant defense systems may exist in both conditions.

Primary open-angle glaucoma vs normal-tension glaucoma: the vascular perspective.

OBJECTIVE: To compare and contrast the presence of ocular and systemic vascular function in patients with newly diagnosed and previously untreated primary open-angle glaucoma (POAG) vs those with normal-tension glaucoma (NTG) and comparable early-stage, functional loss. METHODS: The systemic vascular function of 19 patients with POAG, 19 patients with NTG, and 20 healthy individuals serving as controls was assessed using 24-hour ambulatory blood pressure monitoring, peripheral pulse-wave analysis, and carotid intima-media thickness. Retinal vascular reactivity to flicker light was assessed using dynamic retinal vessel analysis (Imedos, GmbH). RESULTS: Compared with controls, patients with POAG and those with NTG exhibited similarly increased nocturnal systemic blood pressure variability (P = .01), peripheral arterial stiffness (P = .02), carotid intima-media thickness (P = .04), and reduced ocular perfusion pressure (P < .001). Furthermore, on dynamic retinal vessel analysis, both glaucoma groups exhibited steeper retinal arterial constriction slopes after cessation of flicker (P = .007) and a similarly increased fluctuation in arterial and venous baseline diameter (P = .008 and P = .009, respectively) compared with controls. CONCLUSIONS: Patients with POAG or NTG exhibit similar alterations in ocular and systemic circulation in the early stages of their disease process. This finding highlights the importance of considering vascular risk factors in both conditions and raises questions about the current separation of the two conditions into distinct clinical entities.